Clinical Outcome of Transcervical Infusion of a Combination of Procaine Penicillin and Gentamicin in Late-term Pregnant Mares.

Transcervical intrauterine infusion of antibiotics may more effectively treat pathogens associated with fetal and neonatal disease in pregnant mares than standard systemic routes. The objective of this study was to assess the safety of transcervical antibiotic infusion by characterizing the gestational outcome in nine healthy pregnant pony mares following a single transcervical infusion of 2.4 million IU of procaine penicillin and 200 mg of gentamicin in a 10 mL volume during late gestation. Assessment of fetal-placental health was performed through serial measurement of the combined thickness of the uterus and placenta (CTUP) and fetal heart rate and mares and foals were closely monitored in the periparturient period. Fetal heart rate and CTUP remained unchanged after infusion, with no evidence of fluid accumulation or significant increase at the time-points 24, 48, and 72 hours. All mares foaled without complication 12-58 days after antibiotic infusion at a mean gestational age of 322.7 ± 12.7 days. Two out of nine foals displayed signs of mild neonatal maladjustment syndrome that responded to minimal supportive care and all foals survived to weaning without further complications.

Plasma metabolomic profiling of healthy pregnant mares and mares with experimentally induced placentitis.

BACKGROUND: Metabolomics may represent an avenue for diagnosis of equine ascending placentitis. OBJECTIVES: To characterise the plasma metabolomic profile in healthy mares and mares with induced ascending placentitis, with the goal of identifying metabolites with potential clinical value for early diagnosis of placentitis. STUDY DESIGN: Controlled in vivo experiment. METHODS: Placentitis was induced in 10 late-term pregnant pony mares via Streptococcal equi subsp. zooepidemicus inoculation in five mares between days 285 and 290 of gestation, while five mares served as healthy controls. Repeated ultrasound examinations and jugular venipuncture were performed to obtain combined thickness of the uterus and placenta (CTUP) and plasma for NMR spectroscopy. Mares with increased CTUP were diagnosed with placentitis and treated in accordance with published therapeutic recommendations. NMR metabolomic analysis was performed to identify and quantify plasma metabolites at each time point. Concentrations were compared using ANOVA with repeated-measures and PLS-DA analysis. RESULTS: Four hours post-inoculation, a significant increase was detected in the metabolites alanine, phenylalanine, histidine, pyruvate, citrate, glucose, creatine, glycolate, lactate and 3-hydroxyisobutyrate that returned to baseline by 12 hours. On day 4, a significant reduction in the metabolites alanine, phenylalanine, histidine, tyrosine, pyruvate, citrate, glycolate, lactate and dimethylsulfone was seen in infected mares compared with controls. MAIN LIMITATIONS: There were small numbers of mares within groups. In addition, this work compares healthy animals with animals treated with multimodal therapeutics following diagnosis of placentitis without an untreated cohort. CONCLUSIONS: Two phases of metabolite changes were noted after experimental infection: An immediate rise in metabolite concentration involved in energy, nitrogen, hydrogen and oxygen metabolism within 4 hours after inoculation that was followed by a decrease in metabolite concentrations involved in energy and nitrogen metabolism at 4 days, coinciding with ultrasonographic diagnosis of placentitis.

Metabolomic Profile of Allantoic and Amniotic Fluid in Late-term Gestational Mares Characterized by 1H-nuclear Magnetic Resonance Spectroscopy.

The amniotic and allantoic fluid compartments in the mare serve essential roles throughout pregnancy and parturition. Although the global metabolomic profile of amniotic fluid in women has been extensively characterized, current data for equine fetal fluids are limited. Therefore, the goal of this study was to characterize the global metabolomic profile of equine allantoic and amniotic fluid through nuclear magnetic resonance spectroscopy. Fetal fluids were collected between 270 and 295 days of gestation from 12 pregnancies through ultrasound-guided transabdominal puncture. A total of 24 samples (n = 10 allantoic fluid; n = 9 amniotic fluid; n = 5 admixed fluid) were analyzed by one-dimensional proton (1H) and two-dimensional (1H-13 C) nuclear magnetic resonance spectroscopy. Metabolites were integrated and compared between fluid types using a Kruskal-Wallis test at P < .05 significance. A total of 28 distinct metabolites were found in allantoic and admixed fluid, whereas 23 metabolites were identified in amniotic fluid. Allantoic fluid contained significant elevations (P < .05) in the metabolites betaine, creatine, creatinine, citrate, histidine, nitrophenol, tryptophan, π-methylhistidine, and unknown metabolite #1 compared with amniotic fluid, whereas amniotic fluid contained statistically increased concentrations of the metabolite lactate compared with allantoic fluid (P = .003).

Antimicrobial Activity of Ceftiofur and Penicillin With Gentamicin Against Escherichia coli and Streptococcus equi Subspecies zooepidemicus in an Ex Vivo Model of Equine Postpartum Uterine Disease.

The use of antimicrobials for the management of equine uterine disease is commonplace, with antibiotic selection generally based on empirical evidence or in vitro sensitivity results. However, the potential disconnect between these laboratory results and clinical efficacy in the mare raises concern for antibiotic failure and subsequent development of resistant organisms. In this work, we attempt to bridge this gap by using an ex vivo model of the equine postpartum uterus to quantitatively evaluate the antimicrobial activity of two commonly used antibiotic treatments in the mare (ceftiofur and penicillin with gentamicin). The activity of both of these treatments was evaluated in two different fluid environments (standard bacterial culture broth and equine postpartum uterine fluid) against clinical isolates of E. coli and S. zooepidemicus. Although treatment with ceftiofur was effective at reducing growth of S. zooepidemicus in equine postpartum uterine fluid, it did not reduce bacterial growth of E. coli. Treatment with procaine penicillin G with gentamicin achieved at least bacteriostatic activity against E. coli in both fluid types, and bactericidal activity against S. zooepidemicus in both fluid types. The intrauterine infusion of procaine penicillin G with gentamicin in cases of postpartum uterine disease caused by E. coli or S. zooepidemicus is supported by the results of this work.

Pharmacokinetics of Intrarectal Altrenogest in Horses.

Hospitalized pregnant mares being held nil per os (PO) because of medical or surgical events present a dilemma for pregnancy maintenance therapy, which commonly includes oral altrenogest. Rectal administration of medications is a recognized route for achieving systemic concentrations, but there are no data on the pharmacokinetics of rectal altrenogest administration in horses. The purpose of this study was to determine the pharmacokinetics of altrenogest following PO or per rectum (PR) administration in mares. Using a randomized two-way crossover study design, six horses received altrenogest (0.088 mg/kg; PO or PR q 24 hours for 5 days), with a 7-day washout period, and the concentrations of altrenogest were determined by an ultrahigh performance liquid chromatography with tandem mass spectrometry. Plasma concentrations persisted above presumed therapeutic concentrations for a mean of 36 hours (range 24-72 hours) and 5.5 hours (range 3-8 hours) for PO and PR administration, respectively. The calculated half-life (T ½) of PO administration (7.01 ± 3.13 hours) was correspondingly increased when compared to PR administration (2.82 ± 1.07 hours). Relative bioavailability of altrenogest following PR administration was only 5.47%. Altrenogest is rapidly absorbed following PR administration in the horse and reaches therapeutic concentrations, making this a viable method of treatment in NPO mares. The decreased bioavailability and shorter detection time suggest 0.088 mg/kg PR q 4-8 hours would be necessary to maintain therapeutic concentrations over a 24-hour period.